Influenza virus is a member of Orthomyxoviridae family (Murphy and Webster, Orthomyxoviruses, Fields Virology, Third Edition, vol. 1, pp. 1397-1445, 1996). There are three types of influenza viruses designated A, B, and C. The influenza virion contains a segmented negative-sense RNA genome. The influenza virion includes the following proteins: hemagglutinin (HA), neuraminidase (NA), matrix (M1), proton ion-channel protein (M2), nucleoprotein (NP), polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), polymerase acidic protein (PA), and nonstructural protein 2 (NS2) proteins. The NP and the matrix protein M1 are used to classify the influenza virus into group A, B or C.
The HA and NA proteins are envelope glycoproteins. The HA protein is responsible for virus attachment and penetration of the viral particles into the cell and contains the major immunodominant epitopes for virus neutralization and protective immunity. Both HA and NA proteins are considered the most important components for prophylactic influenza vaccines. To date, eighteen different HA subtypes and eleven different NA subtypes have been identified (Tong et al., 2013, PLoS Pathogens, Vol. 9 (10), New World Bats harbor diverse influenza A viruses).
Globally, influenza is the most economically significant respiratory disease in humans, pigs, horses and poultry. Influenza virus is known for its continuous genetic and antigenic changes, which impede effective control of the virus. Of particular concern for prevention of epidemics and pandemics is the emergence of a new subtype of the virus by genetic re-assortment or inter-species transmission.
Recently, influenza outbreaks have occurred in species, e.g., feline and canine, which historically do not carry influenza virus. During 2004 and 2005, outbreaks of respiratory disease in racing greyhounds caused by infection with influenza virus occurred in Florida, eastern and western Iowa, and Texas. Molecular and antigenic analyses of three influenza viruses isolated from outbreaks of severe respiratory disease in racing greyhounds revealed that they are closely related to H3N8 equine influenza virus (Crawford et al., Science, 2005, 310 (5747):482-485; PLOS Pathogens, 2014, 10 (10), e1004455).
U.S. Pat. No. 8,246,962 and Song et al. (2008 Emerg. Infect. Dis., 2008, 14, pp. 741-746) reported an infection of an H3N2 subtype influenza virus in a pet dog in the Republic of Korea. The case was caused by a H3N2 avian-origin canine influenza virus (CIV), which infected dogs successfully through nasal inoculation or contact (respiratory fluid exchange) under experimental conditions.
Li et. al. (Infection, Genetics and Evolution, 2010, 10 (8): 1286-1288) reported four sporadic cases of H3N2 canine influenza in Southern China, which were identified from sick dogs from May 2006 to October 2007. The evolutionary analysis showed that all eight segments of these four viruses are avian-origin and phylogenetically closely related to the H3N2 canine influenza viruses reported earlier in South Korea.
H3N2 canine influenza can be transmitted to cats and cause severe respiratory disease in cats (Song et al., J. Gen. Virol. 2011, 92:23050-2355).
On Mar. 26, 2015, the Chicago Tribune reported an outbreak of canine influenza caused by a new strain of virus identified as H3N2. As of today, the virus has now been detected in dogs in 30 states, including Illinois, Ohio, Wisconsin, Indiana, Iowa, Minnesota, Michigan, California, Massachusetts, Texas, New Jersey, South Dakota, and Georgia.
There were no vaccines available in the U.S. for H3N2 CIV as of June 2015. The H3N8 CIV vaccines currently marketed in the U.S. are unlikely to protect dogs against H3N2 CIV due to the genetic divergence in the HA proteins encoded by the two virus subtypes. Although both viruses encode H3 subtype HAs, the proteins only share about 77% sequence identity at the amino acid level.
Accordingly, there is an urgent need for an effective vaccine against H3N2 influenza infection in canines and felines.